theonellasterone

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: theonellasterone
• 英文别名: (5R,9R,10R,13R,17R)-17-[(2R,5S)-5-ethyl-6-methylheptan-2-yl]-10,13-dimethyl-4-methylidene-2,5,6,7,9,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-one
• 化学式: C₃₀H₄₈O
• 分子量: 424.711
• InChiKey: OIQXLYXVBPOAHN-WYYSBJOASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.8
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  theonellasterone 在 sodium tetrahydroborate 、 cerium(III) chloride 作用下， 以 甲醇 、 苯 为溶剂， 反应 0.33h， 以72 mg的产率得到theonellasterol
  参考文献：
  名称：

  Marine Natural Products. XXX. Two New 3-Keto-4-methylene Steroids, Theonellasterone and Conicasterone, and a Diels-Alder Type Dimeric Steroid Bistheonellasterone, from the Okinawan Marine Sponge Theonella swinhoei.

  摘要：

  从冲绳海洋海绵Theonella swinhoei中分离出两种新的3-酮-4-亚甲基类固醇，即theonellasterone（3）和conicasterone（4），以及一种Diels-Alder型二聚类固醇，即bistheonellasterone（5），以及两种已知的4-亚甲基固醇，即theonellasterol（1）和conicasterol（2）。这些类固醇的结构已经根据化学和物理化学证据得到阐明。Bistheonellasterone（5）被认为是通过theonellasterone（3）及其Δ4-异构体的Diels-Alder环加成生物合成的。非常有趣的是，在光学显微镜下，theonellasterone（3）和conicasterone（4）被看作是沉积在新鲜海洋海绵组织中的晶体。

  DOI：

  10.1248/cpb.40.1773
• 作为产物：
  描述：

  theonellasterol 在 pyridinium chlorochromate 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以100%的产率得到theonellasterone
  参考文献：
  名称：

  Preliminary Structure-Activity Relationship on Theonellasterol, a New Chemotype of FXR Antagonist, from the Marine Sponge Theonella swinhoei

  摘要：

  Using theonellasterol as a novel FXR antagonist hit, we prepared a series of semi-synthetic derivatives in order to gain insight into the structural requirements for exhibiting antagonistic activity. These derivatives are characterized by modification at the exocyclic carbon-carbon double bond at C-4 and at the hydroxyl group at C-3 and were prepared from theonellasterol using simple reactions. Pharmacological investigation showed that the introduction of a hydroxyl group at C-4 as well as the oxidation at C-3 with or without concomitant modification at the exomethylene functionality preserve the ability of theonellasterol to inhibit FXR transactivation caused by CDCA. Docking analysis showed that the placement of these molecules in the FXR-LBD is well stabilized when on ring A functional groups, able to form hydrogen bonds and π interactions, are present.

  DOI：

  10.3390/md10112448

文献信息

• Theonellasterone, a steroidal metabolite isolated from a Theonella sponge, protects peroxiredoxin-1 from oxidative stress reactions
  作者：L. Margarucci、M. C. Monti、A. Tosco、R. Esposito、A. Zampella、V. Sepe、M. Mozzicafreddo、R. Riccio、A. Casapullo

  DOI：10.1039/c4cc09205h

  日期：——

  Peroxiredoxin-1, a key enzyme in the cellular detoxification pathway, has been identified through a chemoproteomic approach as the main partner of theonellasterone, a marine bioactive metabolite. A combination of chemical and biochemical assays disclosed its mechanism of action at the molecular level.

  Peroxiredoxin-1是细胞排毒途径中的关键酶，已通过化学计量学方法鉴定为海洋生物活性代谢产物theonellasterone的主要伴侣。化学和生化分析的组合揭示了其在分子水平上的作用机理。
• Marine Natural Products. XXX. Two New 3-Keto-4-methylene Steroids, Theonellasterone and Conicasterone, and a Diels-Alder Type Dimeric Steroid Bistheonellasterone, from the Okinawan Marine Sponge Theonella swinhoei.
  作者：Motomasa KOBAYASHI、Kazuyoshi KAWAZOE、Taketo KATORI、Isao KITAGAWA

  DOI：10.1248/cpb.40.1773

  日期：——

  Two new 3-keto-4-methylene steroids, theonellasterone (3) and conicasterone (4), and a Diels-Alder type dimeric steroid, bistheonellasterone (5), were isolated together with two known 4-methylene sterols, theonellasterol (1) and conicasterol (2), from the Okinawan marine sponge Theonella swinhoei. The structures of these steroids have been elucidated on the basis of chemical and physicochemical evidence. Bistheonellasterone (5) is considered to be biosynthesized through a Diels-Alder cycloaddition of theonellasterone (3) and its Δ4-isomer. Very interestingly, theonellasterone (3) and conicasterone (4) were seen under an optical microscope as crystals deposited in the tissue of fresh marine sponge.

  从冲绳海洋海绵Theonella swinhoei中分离出两种新的3-酮-4-亚甲基类固醇，即theonellasterone（3）和conicasterone（4），以及一种Diels-Alder型二聚类固醇，即bistheonellasterone（5），以及两种已知的4-亚甲基固醇，即theonellasterol（1）和conicasterol（2）。这些类固醇的结构已经根据化学和物理化学证据得到阐明。Bistheonellasterone（5）被认为是通过theonellasterone（3）及其Δ4-异构体的Diels-Alder环加成生物合成的。非常有趣的是，在光学显微镜下，theonellasterone（3）和conicasterone（4）被看作是沉积在新鲜海洋海绵组织中的晶体。
• Preliminary Structure-Activity Relationship on Theonellasterol, a New Chemotype of FXR Antagonist, from the Marine Sponge Theonella swinhoei
  作者：Valentina Sepe、Raffaella Ummarino、Maria D'Auria、Orazio Taglialatela-Scafati、Simona Marino、Claudio D'Amore、Barbara Renga、Maria Chini、Giuseppe Bifulco、Yoichi Nakao、Nobuhiro Fusetani、Stefano Fiorucci、Angela Zampella

  DOI：10.3390/md10112448

  日期：——

  Using theonellasterol as a novel FXR antagonist hit, we prepared a series of semi-synthetic derivatives in order to gain insight into the structural requirements for exhibiting antagonistic activity. These derivatives are characterized by modification at the exocyclic carbon-carbon double bond at C-4 and at the hydroxyl group at C-3 and were prepared from theonellasterol using simple reactions. Pharmacological investigation showed that the introduction of a hydroxyl group at C-4 as well as the oxidation at C-3 with or without concomitant modification at the exomethylene functionality preserve the ability of theonellasterol to inhibit FXR transactivation caused by CDCA. Docking analysis showed that the placement of these molecules in the FXR-LBD is well stabilized when on ring A functional groups, able to form hydrogen bonds and π interactions, are present.